ZAR1L

Chr 13

zygote arrest 1 like

Also known as: Z3CXXC7, ZAR2

NCBI Gene: 646799 ENSG00000189167 UniProt: A6NP61

This protein binds maternal mRNAs and regulates their storage, translation and degradation during oocyte maturation, likely through formation of phase-separated compartments. Mutations in ZAR1L cause autosomal recessive oocyte maturation defects and female infertility. The gene shows moderate constraint against loss-of-function variants, consistent with its essential role in early reproductive development.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the ZAR1 family that is predominantly expressed in oocytes and early embryos. The protein may function as an RNA regulator in early embryos. [provided by RefSeq, Apr 2010]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.69

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.69LOEUF

pLI 0.099

Z-score 2.37

OE 0.30 (0.15–0.69)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.69Z-score

OE missense 0.65 (0.56–0.76)

123 obs / 188.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.30 (0.15–0.69)

0≤0.351.4

Missense OE?0.65 (0.56–0.76)

0≤0.61.4

Synonymous OE?0.79

0≤1.21.6

LoF obs/exp: 4 / 13.3Missense obs/exp: 123 / 188.2Syn Z: 1.51

Background carrier burden — how many people carry a rare variant somewhere in ZAR1L?

gnomAD v4 · ~700k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

428 rare PASS variants

Rare truncating (LoF)

1 in 6,800

38 rare PASS variants

Rare synonymous (reference)

1 in 760

208 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZAR1L. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~540k	1 in 300	1 in 5,500
South Asian	~40k	1 in 140	1 in 6,500
Remaining (unassigned)	~29k	1 in 150	≈ 1 in 14,000
European (Finnish)	~25k	1 in 960	≈ 1 in 12,000
African / African American	~21k	1 in 110	≈ 1 in 5,700
East Asian	~18k	1 in 120	≈ 1 in 8,900
Admixed American	~18k	1 in 200	≈ 1 in 18,000
Ashkenazi Jewish	~13k	1 in 510	none seen
Middle Eastern	~2,852	1 in 170	≈ 1 in 2,800

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓